Title Neurodevelopmental Pathways Linking Physical Abuse and Affective Dysregulation Project Summary/Abstract Exposure to physical abuse is a significant risk factor for the development of affective disorders later in life. Though this major public health issue has been well studied and well replicated, much remains unclear about the mechanisms connecting abuse and later depression and anxiety. Past work has primarily relied on self- report measures of maltreatment, which may have significant and confounding biases. Furthermore, previous research studies focused on neurobiological alterations after abuse have only examined one neurobiological marker of risk in the same individuals (such as brain function, but not brain structure). Here, our work leverages existing data collected as part of the Pittsburgh Youth Study, a longitudinal project that followed two cohorts of boys through childhood, adolescence, and into adulthood. At the most recent follow-up, neuroimaging data were collected on a subset of 205 men. For this project, we will focus on corticolimbic circuitry (including the amygdala, portions of the prefrontal cortex, and hippocampus) in relation to physical abuse. This brain circuitry is theorized to be central to processing of emotional and social information, core dysregulated elements in depression and anxiety. Identifying the neurobehavioral bases of these links is crucial to our understanding of the developmental sequelae of abuse, the emergence of depression and anxiety after maltreatment, and the development of intervention strategies aimed at ameliorating the long-term effects of physical abuse. To these ends, this application has two specific aims. First, we will investigate linkages between neurobiology, physical abuse, and symptoms of affective psychopathology. We hypothesize that physical abuse will be related to heightened amygdala functional activity. We additionally predict that abused individuals with heightened amygdala functional activity, as well as reduced amygdala-ventromedial prefrontal cortex connectivity will show the greatest levels of depression and anxiety. Second, we aim to investigate how the chronicity of abuse may impact corticolimbic brain structure and function (again, assessed with multiple methods of MRI). For this aim, we will use latent class-modeling and multivariate MRI analytic tools to examine differences in amygdala and ventromedial prefrontal structure, function, and connectivity. By leveraging rich prospective longitudinal data, we may be able to more accurately characterize foundational principles of brain organization, and more directly connect neurobiology to experiences of abuse. With an alarming amount of children suffering abuse, investigation of these links is important and timely. Our proposed work represents an unprecedented opportunity to understand the neurobiological sequelae of physical abuse. This work can also aid in answering basic science questions, such as how environmental experience influences long-term brain development. Furthermore, this work can powerfully inform our understanding of mood dysregulation in relation to physical abuse.